This grant will develop wearable full-head high-density diffuse optical tomography (HD-DOT) for mapping human brain function longitudinally at the bedside in clinical settings. Functional neuroimaging of healthy adults has enabled mapping of brain functions and revolutionized cognitive neuroscience. However, the logistics of traditional functional brain scanners (e.g., fMRI) restrict use to single snap shot application and therefore provide only a very limited assessment during rapidly evolving clinical scenarios. Thus there is a need for a bedside functional imaging modality capable of monitoring neurological status longitudinally. Optical imaging has long held promise as a bedside neuroimaging technique. However, image quality has been lacking, particularly in comparison to the gold standard of functional brain imaging - fMRI. Moreover, traditional functional mapping requires subjects to perform tasks, which is very limiting in clinical populations. Two recent developments have improved the outlook. First, high- density diffuse optical tomography (HD-DOT) has improved image quality dramatically. When matched within subjects against fMRI, HD-DOT now can obtain localization errors <5mm, and point spread functions <15 mm FWHM, sufficient to localize functions to gyri. Second, emerging methods for mapping the functional connectivity of intrinsic brain activity (fcDOT) now can assay cerebral function without requiring task performance. Despite these advances, clinical application of fcDOT has been limited by a barrier imposed by a coverage-vs-wearability tradeoff. The central photonic challenges are optical sensitivity - which biases design towards larger/heavier fibers - and coverage - which biases design towards a larger number of fibers. Related challenges exist in registration of data to anatomy and removal of motion artifacts. This proposal will address these technological challenges and develop wearable whole-head fcDOT for longitudinal bedside imaging. Aim 1 addresses photonics/ergonomics challenges with a new detection strategy for DOT that will enable use of smaller fibers (<1/30 of current standard) and development of a novel full-head low-profile wearable HD-DOT cap. Aim 2 will develop a new set of software tools to enable high-fidelity imaging in the clinic. Aim 3 will develop and validate fcDOT for mapping brain networks in healthy subjects and chronic stroke with evaluations against fcMRI and neurocognitive testing. Aim 4 will establish the feasibility of longitudinal fcDOT mapping in acute stroke by measuring the relationship between fcDOT and NIH Stroke Scale (NIHSS). These studies will represent the culmination of several advances in functional neuroimaging made possible by the research teams' unique combination of clinical and technical expertise across the domains of neurology, functional neuroimaging and biomedical optics.